Regulation of Na₊/K₊ ATPase transport velocity by RNA editing

Because firing properties and metabolic rates vary widely, neurons require different transport rates from their Na⁺/K⁺ pumps in order to maintain ion homeostasis. In this study we show that Na⁺/K⁺ pump activity is tightly regulated by a novel process, RNA editing. Three codons within the squid Na⁺/K⁺ ATPase gene can be recoded at the RNA level, and the efficiency of conversion for each varies dramatically, and independently, between tissues. At one site, a highly conserved isoleucine in the seventh transmembrane span can be converted to a valine, a change that shifts the pump's intrinsic voltage dependence. Mechanistically, the removal of a single methyl group specifically targets the process of Na⁺ release to the extracellular solution, causing a higher turnover rate at the resting membrane potential.